Numerous methods have been used to produce microneedles attached to a substrate for the purpose of application through the skin of a patient. These are uniform regular structures produced using various moulding techniques. It has been proposed that the microneedles themselves may be produced from a formulation of the drug. On application to the skin of a patient, the needles break and remain in the skin, where the formulation dissolves and the active substance is absorbed into the blood stream.
In published literature it is known that particles such as platelets and other shapes have also been produced using various techniques including lithographic and micro-moulding, micro-replication and imprinting techniques, in order to produce particles of defined (and often large) surface areas for enhanced drug solubility for example, with subsequent incorporation into depot injections, oral solutions or compressed into tablets and filled into capsules.
The main barrier to the delivery of drugs through the skin is the stratum corneum, which is a tough outer layer of dead skin cells. A further route for delivery of a drug into the body of a patient, especially for treatment of diseases of the eye, is through the surface of the cornea of the eye. For the purposes of this specification, that route is included within the term “transdermal”.
In conventional tabletting, the granules are produced using an elaborate process of producing a wet or dry mass of the drug and excipients followed by size reduction using mechanical means amongst others, and using spray-drying, freeze-drying or further processing as required such as coating the particles, followed by their subsequent storage either in the granular form (for enhanced dissolution) or compressed into tablets (since the granules provide the correct bulk density and compression properties for processing into tablets).
Particles of drug are also described in published patent application WO 2012/020261, which further describes a method for producing said angular particles by forming a film of the drug which is dried and size reduced using some form of grinding technique. Particles of the drug formulation may be produced as individual separate entities as described in WO 2012/020261. These particles may be used for direct insertion into the skin or cornea of a patient, or the particles may be used as a means of enhancing the surface area and thus solubility of a drug. The method of preparing such particles through the formation of a film followed by drying and milling will lead to a large range of particle sizes/lengths. It may be preferable to produce such particles within narrow dimensional profiles using a process that leads to high yields within narrower particle size profiles.